Scandinavian Journal of Rheumatology最新文献

Objective: The aim of this study was to investigate associations between sex and treatment response and persistence in patients with rheumatoid arthritis (RA) initiating their first tumour necrosis factor inhibitor (TNFi).

Method: This Danish nationwide cohort study included RA-patients starting their first TNFi treatment between 2006 and 2022. Overall and age-specific treatment response was compared across sexes at 4 and 12 months. Treatment persistence was investigated using survival analysis.

Results: In total, 7789 RA-patients were identified; 75% were females. Females had slightly smaller ∆DAS28-CRP compared to males after 12 months, mainly due to less reduction of swollen joint count (SJC) and CRP. At 12 months the crude proportion of males with good response was higher (62%) than in females (55%), adjusted RR 1.14 (95% confidence interval (CI) 1.06; 1.23). The adjusted hazard ratio for treatment termination within first year was 0.82 (95% CI 0.73; 0.92) in males versus females. The median treatment persistence for individuals aged <50 years was 1.6 years (95% CI 1.4; 1.8) in females and 3.2 years (95% CI 2.6; 4.0) in males. The same difference was not seen in patients aged > 50 years.

Conclusion: Despite similar baseline disease activity, females had a lower chance than males of achieving good response 4 and 12 months after starting treatment with first TNFi. The sex difference in DAS28-CRP improvement is caused by a greater decrease in CRP and SJC among males. Further, females had an increased risk of discontinuation, especially among patients aged < 50 years.

Objective: To evaluate the prognostic significance and safety of therapeutic plasma exchange (TPE) in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) with severe organ or system involvement.

Method: Data of patients diagnosed with AAV between 2011 and 2021 were evaluated retrospectively. Patients with baseline estimated glomerular filtration rate (eGFR) ≤ 50 mL/min/1.73m² or diffuse alveolar haemorrhage (DAH) were included in the analysis (n = 71). Patients who underwent TPE were compared with others in the groups formed after two models of propensity score matching (PSM). Initial PSM was performed according to the presence of DAH, age, gender, eGFR, and BVAS. A data-driven approach was conducted for the second model.

Results: In the initial PSM cohort (n = 48), the remission rate at 6 months was lower in the TPE group (p = 0.04). There were no significant differences in mortality and improvement of eGFR at 6 and 12 months. No severe complications due to TPE were observed. Rates of serious infections (SIs) and end-stage renal disease (ESRD) at 12 months were higher in the TPE group (p = 0.016 and 0.02, respectively). Data-driven PSM analysis (n = 44) revealed no significant differences between groups.

Conclusion: We did not demonstrate a positive effect of TPE on remission, ESRD, and mortality in AAV in this study. Despite low short-term complication rates, the increased risk of SIs possibly associated with ESRD was remarkable. The limited long-term benefits of TPE should be carefully weighed against its associated risks when selecting patients for treatment.

Objective: Recent studies suggest that dyslipidaemia may play a critical role in the progression of cardiovascular disease in Takayasu arteritis (TA), although the exact relationship between dyslipidaemia and TA disease activity remains unclear, which is the focus of this study.

Method: We evaluated dyslipidaemia and atherosclerosis in a cohort of untreated female patients. Fifty untreated female patients with TA (median age 30 years) and 98 healthy controls matched for age and body mass index (median age 30 years) were assessed for lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), ApoB, ApoE, lipoprotein(a)], inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)], and atherosclerotic plaque frequency.

Results: TA patients exhibited significantly higher levels of TG and the non-HDL-C/HDL-C ratio than the control group, whereas TC, HDL-C, LDL-C, and ApoA1 levels were significantly lower. Pearson's correlation analysis indicated a positive correlation between CRP and ApoB, as well as the non-HDL-C/HDL-C ratio, and negative correlations with TG, HDL-C, and ApoA1. Atherosclerotic plaques were detected in 14.3% of the TA patients. Multivariate regression analysis revealed that the presence of atherosclerotic plaques was associated only with age, independent of inflammatory markers and lipoprotein levels.

Conclusion: The results of this study indicate that untreated female TA patients exhibit a markedly dysregulated serum lipid profile. Atherosclerosis in early TA was not related to lipids or markers of inflammation.

Objective: Macrophages play a crucial role in gouty arthritis; however, the relationship between non-inflammatory macrophages (M0) and different stages of gout remains unclear. This study aimed to investigate the phagocytosis, hydrolysis, and subsequent cytokine secretion of monosodium urate (MSU) by non-inflammatory macrophages in patients in different stages of gout.

Method: Non-inflammatory macrophages were derived from monocytes through stimulation with macrophage colony-stimulating factor (M-CSF) for a duration of 10 days. The study included patients with asymptomatic hyperuricaemia, intercritical gout, tophaceous gout, and a normal control group. The phagocytic and hydrolytic capabilities of non-inflammatory macrophages were measured using flow cytometry based on the increase in side-scatter area. In addition, to evaluate the relationship between the hydrolysis capability of non-inflammatory macrophages and subsequent inflammation, we cultured them with lipopolysaccharide (LPS) and/or MSU.

Results: We discovered that M0 macrophages were capable of phagocytosing and hydrolysing MSU crystals in various stages of gout, including the control group. Patients with asymptomatic hyperuricaemia exhibited the most pronounced phagocytic and hydrolytic capabilities, surpassing even those of the normal control group. The presence of MSU alone did not induce the secretion of pro-inflammatory cytokines. However, in experiments where M0 macrophages were stimulated with LPS and/or MSU, the phagocytic and hydrolytic abilities of M0 macrophages were correlated with inflammatory cytokine elevation.

Conclusion: The efficient phagocytosis and hydrolysis of MSU crystals by M0 macrophages suggest their role in maintaining the non-inflammatory stage of gout. Our findings suggest that non-inflammatory macrophages play a role in gout.

Objective: To compare the risk of cardiovascular disease (CVD) and gastrointestinal bleeding (GIB) between celecoxib and non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) in patients with ankylosing spondylitis (AS).

Method: In this nationwide retrospective cohort study using the Korean Health Insurance Review and Assessment database, adult AS patients who received newly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) continuously for ≥ 30 days (celecoxib or nsNSAIDs) between 2013 and 2017 were evaluated. The co-primary outcomes were the occurrence of composite CVD events, including hospitalization for myocardial infarction, ischaemic heart disease, stroke, transient ischaemic attack, heart failure, and coronary revascularization; and composite GIB, including hospitalization for upper and lower GIB. Propensity score (PS) matching was used to correct for baseline differences between the celecoxib- and nsNSAID-treated groups.

Results: We identified 3164 celecoxib-treated and 18924 nsNSAID-treated patients with AS. After 1:1 PS matching, 3047 patients with AS were assigned to each of the celecoxib- and nsNSAID-treated groups. The incidence of composite CVD and GIB was 18.2/1000 person-years and 6.5/1000 person-years in celecoxib-treated and 15.1/1000 person-years and 7.3/1000 person-years in nsNSAID-treated patients, respectively. Compared to the nsNSAID-treated group, the hazard ratios of composite CVD and GIB in the celecoxib-treated group were not significant, with values of 1.17 (p = 0.499) and 0.87 (p = 0.696), respectively. There were no significant differences in the risk of each component of the composite CVD and GIB between the two groups.

Conclusion: We did not find significant differences in the risks of CVD and GIB between celecoxib and nsNSAIDs in AS patients.

Objective: Methotrexate (MTX) is widely used as first-line treatment in psoriatic arthritis (PsA). Despite the variable efficacy of MTX in PsA compared to newer therapeutic agents, its affordability and availability make it crucial, especially in resource-limited healthcare settings. Identification of factors associated with MTX non-response could facilitate early redirection to more effective therapy. This study aimed to identify baseline clinical, demographic, and psychosocial variables associated with non-response 3 months after MTX initiation in a real-world, treatment-naïve PsA patient cohort.

Method: Recently diagnosed, disease-modifying anti-rheumatic drug-naïve PsA patients were included. Treatment response was defined by attaining minimal disease activity 3 months after initiation of MTX monotherapy. A multivariate logistic regression analysis was performed, including sensitivity analysis. Missing variables were imputed through multiple imputations.

Results: In total, 287 patients were included, of whom 199 (69%) were non-responders. The median dose of MTX was 19.5 (interquartile range 15-25) mg/week. Worse baseline functioning (Health Assessment Questionnaire) [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.13-0.60], higher tender joint count in 68 joints (OR 0.91, 95% CI 0.84-0.97), and higher depression scores (Hospital Anxiety and Depression Scale) (OR 0.88, 95% CI 0.78-0.99) were associated with a lower response rate to MTX at 3 months.

Conclusion: Our findings highlight the need for a comprehensive approach to managing patients with PsA. This involves addressing modifiable risk factors, such as depression, alongside controlling PsA disease activity. Further research is warranted to evaluate whether this integrated strategy could improve treatment efficacy and overall patient outcomes.

Objectives: Rheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. Pro-inflammatory cytokines produced by various immune cells drive the chronic inflammatory processes that lead to joint damage. Many drugs are available for the treatment of RA, but a significant proportion of patients do not respond adequately to them and/or have severe adverse effects. Accordingly, there is an urgent need for new therapeutics for RA. Therefore, we tested pristimerin, a natural triterpenoid, for its anti-arthritic activity in experimental RA.

Method: Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice. After the onset of arthritis, mice were injected daily intraperitoneally with pristimerin or vehicle for 9 days. The severity of clinical arthritis was graded and further validated by micro-computed tomography and histological examination of the hind paws. Defined mediators of arthritogenic processes were quantified by gene expression in the spleen and further validated by immunohistochemistry of paws.

Results: We observed that pristimerin can effectively control arthritis progression in CAIA mice. A preliminary exploration of the mechanisms showed that pristimerin targeted key pro-inflammatory cytokines and chemokines, along with specific mediators of angiogenesis, bone remodelling, and cellular signalling, including the Notch signalling pathway.

Conclusions: This is the first report on pristimerin for its use in the treatment of antibody-induced arthritis and for the targeting of Notch pathway in arthritis by this triterpenoid. As pristimerin can control the effector phase of arthritis, our results are promising for the translation of this experimental therapy to RA patients.